EFFECTIVENESS OF DRUGS IN ANIMALS EXPOSED TO MIXED GAMMA-NEUTRON RADIATIONS. V. BARBITURATES.
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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The plasma disappearance half-times of barbital, hexobarbital, and pentobarbital, and the plasma and cerebrospinal fluid disappearance half-times of 14C labeled pentobarbital were determined in male monkeys Macaca mulatta. These half-time values were compared to those obtained from monkeys which had received 1500-, 5000-, or 10,000-rad doses of mixed gamma-neutron radiations. A radiation dose-related increase of plasma disappearance half-times for all drugs was evident with a significant increase for barbital after 5000 rads P.001 and hexobarbital after 10,000 rads P.05. Cerebrospinal fluid disappearance half-time of pentobarbital was significantly prolonged in the monkeys receiving 5000 rads. Irradiated monkeys also had prolonged duration of sleep when compared with their preirradiation results. These results are interpreted as indicating 1 blood-brain barrier permeability for some barbiturates is altered in irradiated monkeys, 2 radiation causes a greater decrease in renal excretion of barbiturates than in detoxification of barbiturates by liver enzymes, 3 increased duration of effectiveness of barbiturates in irradiated monkeys is related to decreased excretion, decreased drug metabolism, and increased drug concentration in the central nervous system. Author